chr10-117545494-C-T

Variant names:

• chr10-117545494-C-T
• rs8192640
• NM_004098.4:c.407-138C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004098.4(EMX2):​c.407-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,072,236 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.017 (162 hom.)
• Consequence: EMX2 NM_004098.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 2 publications found

Genes affected

EMX2 (HGNC:3341): (empty spiracles homeobox 2) This gene encodes a homeobox-containing transcription factor that is the homolog to the 'empty spiracles' gene in Drosophila. Research on this gene in humans has focused on its expression in three tissues: dorsal telencephalon, olfactory neuroepithelium, and urogenetial system. It is expressed in the dorsal telencephalon during development in a low rostral-lateral to high caudal-medial gradient and is proposed to pattern the neocortex into defined functional areas. It is also expressed in embryonic and adult olfactory neuroepithelia where it complexes with eukaryotic translation initiation factor 4E (eIF4E) and possibly regulates mRNA transport or translation. In the developing urogenital system, it is expressed in epithelial tissues and is negatively regulated by HOXA10. Alternative splicing results in multiple transcript variants encoding distinct proteins.[provided by RefSeq, Sep 2009]

EMX2 Gene-Disease associations (from GenCC):

• schizencephaly

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0133 (2024/152330) while in subpopulation NFE AF = 0.0204 (1390/68024). AF 95% confidence interval is 0.0195. There are 26 homozygotes in GnomAd4. There are 948 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2024 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	NM_004098.4	MANE Select	c.407-138C>T		intron	N/A	NP_004089.1	Q04743-1
	EMX2	NM_001165924.2		c.406+1821C>T		intron	N/A	NP_001159396.1	Q04743-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMX2	ENST00000553456.5	TSL:1 MANE Select	c.407-138C>T		intron	N/A	ENSP00000450962.3	Q04743-1
	EMX2	ENST00000546446.2	TSL:1	n.366-138C>T		intron	N/A
	EMX2	ENST00000442245.5	TSL:2	c.406+1821C>T		intron	N/A	ENSP00000474874.1	Q04743-2

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2026 AN: 152212 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0204

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.0168 AC: 15430 AN: 919906 Hom.: 162 AF XY: 0.0166 AC XY: 7675 AN XY: 461226

African (AFR) AF: 0.00247 AC: 51 AN: 20638

American (AMR) AF: 0.0101 AC: 226 AN: 22406

Ashkenazi Jewish (ASJ) AF: 0.00972 AC: 165 AN: 16980

East Asian (EAS) AF: 0.0000604 AC: 2 AN: 33110

South Asian (SAS) AF: 0.0113 AC: 641 AN: 56876

European-Finnish (FIN) AF: 0.0192 AC: 854 AN: 44398

Middle Eastern (MID) AF: 0.0182 AC: 53 AN: 2916

European-Non Finnish (NFE) AF: 0.0188 AC: 12812 AN: 681526

Other (OTH) AF: 0.0152 AC: 626 AN: 41056

GnomAD4 genome AF: 0.0133 AC: 2024 AN: 152330 Hom.: 26 Cov.: 33 AF XY: 0.0127 AC XY: 948 AN XY: 74486

African (AFR) AF: 0.00284 AC: 118 AN: 41574

American (AMR) AF: 0.0142 AC: 217 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4832

European-Finnish (FIN) AF: 0.0185 AC: 197 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0204 AC: 1390 AN: 68024

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.0204 Hom.: 9

Bravo AF: 0.0123

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.9
DANN	Benign	0.84
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8192640; hg19: chr10-119305005;